FDA accelerated approvals targeted for revamp in House Energy and Commerce committee chair's new bill

The chairman of the House Committee on Energy and Commerce is taking the FDA’s accelerated approval pathway to task. 

Frank Pallone Jr., D-New Jersey, on Monday unveiled the Accelerated Approval Integrity Act, which seeks to ensure drugs that enjoy a quick trip through the regulator offer “proven clinical benefit” to patients. 

“[U]nder the current system, some products have been allowed to stay on the market for far too long without clinical trials that demonstrate a real clinical benefit for patients,” Pallone said in a statement. “Patients deserve to know that the drugs they are taking are safe and effective.” 

The FDA’s accelerated approval pathway lets the agency base approvals on surrogate endpoints, such as protein levels or tumor shrinkage, rather than a demonstrated clinical benefit, like extending patients’ lives. The route helps certain drugs for diseases with unmet need, like some types of cancers and rare diseases, reach patients sooner. But companies with these drugs are required to run confirmatory trials after snagging the accelerated green light. 

If those studies don’t bear fruit, the FDA has procedures in place to remove the product from the market. “However, as multiple witnesses at a February Health Subcommittee hearing testified, these existing tools are cumbersome, resource-intensive and seldom used,” Pallone’s office said in a release. 

Pallone’s bill would provide the FDA with a number of additional authorities to swiftly follow up on meds that win accelerated approval. 

The bill would codify requirements for manufacturers to conduct post-approval studies on drugs that win accelerated approval. It would also require manufacturers to confirm with the FDA how the studies will be conducted before the agency can grant a speedy green light. 

The bill would allow the FDA to require studies to be underway at the time of approval, too, and it would demand more frequent updates on post-approval trials. 

“The bill would also streamline the process for taking products off the market if no clinical benefit is proven in a timely manner,” Pallone continued in his statement. 

If signed into law, the Accelerated Approval Integrity Act would outline expedited procedures for withdrawing approval, “which would include due notice and opportunity for a written appeal to FDA, an opportunity for public comment and may include FDA convening and consulting an advisory committee,” Pallone’s office said. 

Additionally, the bill would specify instances in which an accelerated approval can be withdrawn, which could come down to a manufacturer’s failure to hit study enrollment targets, milestones or simply completing the trial on time. 

The bill would move to automatically expire accelerated approvals one year after post-approval studies are due to wrap up “and in no case later than five years after approval, unless the post-marketing study has been completed and verified the clinical benefit or the Secretary of Health and Human Services determines that adequate progress has been made.” 

Finally, the bill would empower the FDA to ask for additional information on accelerated approval drugs’ labels and levy penalties if companies fail to submit reports or act without “due diligence” on post-approval studies. 

Accelerated approvals have been mounting in recent years, but not always without controversy. Look no further than Biogen’s Alzheimer’s disease drug Aduhelm, which won a speedy approval in 2021 after it was rejected by an FDA expert panel the previous November. The drug’s approval hinged on its ability to decrease amyloid plaques in the brain, which sparked a wide debate over the FDA’s acceptance of what is considered a questionable surrogate marker.

Now, Biogen has been given nine years to complete a confirmatory study to prove its drug’s benefit, though the pharma has said it’s hoping to get initial data out in about half that time. 

Meanwhile, last March, the FDA summoned experts on its oncologic drugs advisory committee to discuss six indications added to drug labels on an accelerated basis that ultimately failed in confirmatory trials. Specifically, the experts homed in on three indications for Merck’s Keytruda, two for Roche’s Tecentriq and one for Bristol Myers Squibb’s Opdivo. 

Prior to that meeting, the FDA convinced PD-1/L1 players Merck & Co., BMS, Roche and AstraZeneca to remove four indications from their cancer meds' labels.

Pallone isn’t the only one campaigning for an accelerated approval revamp. Recently confirmed U.S. FDA Commissioner Robert Califf, M.D., last month clinched the support of Sen. Ron Wyden, D-Oregon, by promising to reform the agency’s speedy approval pathway. 

“[I]t is incumbent upon FDA to ensure that the work does not end with the initial approval,” Califf said in a response to Wyden.